Saturday, September 22, 2012

Day 2 versus Day 5 transfers

When blastocyst transfers were first introduced in the IVF clinic, there was a lot of hope and hype and excitement . We felt ( or were led to believe) that if we could grow embryos up to Day 5 in the incubator and then transfer them into the uterus, the implantation rates would increase . It was logical to assume that blastocyst transfers would improve IVF success rates .Remember that a Day 2 or Day 3 embryo does not belong in either the uterus or the test tube – it should actually be in the fallopian tube ! It was only because we were not able to grow embryos satisfactorily upto Day 5 in the IVF lab that we were forced to do Day 2 and Day 3 transfers in the early days of IVF. However, as time progressed , we have learned a lot about how to keep embryos happy in the IVF lab , thanks to improvements in incubator technology ; in the formulation of IVF culture medium ; as well as the embryologist’s expertise. This is why it is now possible for most good IVF labs to happily grow embryos in vitro to blastocysts.

In spite of this , there are still many labs which still transfer on day two or three. Why do they do so ?Paradoxically, I do not believe that a blastocyst transfer will necessarily increase pregnancy rates . Let me explain why. While it is true that a blastocyst transfer allows us to select the best embryos ( because we can allow the Day 2 and Day 3 embryos to compete amongst themselves in the incubator and then select the ones which grow the best in vitro at Day 5) , rather than play eenie- meenie-mina-moh when trying to select the top quality embryo on Day 2 or 3. This is because sometimes all the 8 embryos on Day 2 may look perfect , with four equal cells and no fragments. It then become very difficult to predict which of these has the best chances of implantation. Obviously , not all of them will continue to divide to form blastocysts . Instead of selecting embryos at random , and not doing a very good job with embryo selection , doing a blastocyst transfer allows us to preferentially select those embryos, which are more likely to implant and become a baby. This means that the major benefit of blastocyst transfer is that it allows us to improve our ability to select the top quality embryo . If an embryo is going to arrest on Day 3 or Day 4, there’s no point in transferring this into the uterus on Day 2, even if it does look perfect ! Having said this , do remember that if an embryo is going to become a baby , then it will do so , whether we transfer on Day 2 or Day 5. After all, culturing the embryo for three additional days in the incubator will not increase the chances of its implanting !

So does this leave you more confused than ever as to whether Day 5 is better than Day 2 ? It actually should not ! Any good IVF clinic should be able to grow embryos up to blastocysts routinely, so that they can then pick and choose what is best for the individual patient . This decision needs to be based on multiple factors: for example , how many IVF cycles has the patient failed earlier ; whether there are enough eggs ; whether the embryo quality is good enough , and so on. However , if your IVF lab is not good enough , and cannot grow embryos up to blastocysts , and therefore transfers all embryos routinely for all patients only on day 2 or day 3, this is very worrisome . It's important for doctors to be able to offer individualized treatment , so they can select what's best for each patient , but doing this requires a lot of experience and expertise .Being able to grow embryos up to blastocysts allows doctors much more flexibility , so they can pick and choose the right treatment option for each patient. Thus, if your clinic wants to transfer five Grade A Day 2 embryos , then you should worry , because any clinic which wants to transfer so many embryos at one time is most probably not very confident about their embryo implantation rate. This is why they may resort to transferring too many embryos , in order to increase their pregnancy rates ! However, the risk of transferring too many embryos is that you end up increasing the risk of a multiple pregnancy.

One of the questions many patients ask is – If I only have 2 embryos , then isn't it really risky to grow them to blastocyst ? Suppose we culture them in vitro , and they fail to grow ? If they arrest , and I do not have any blastocysts at all, then my chances of getting pregnant are zero. Isn’t it better to transfer something, rather than nothing ? After all, isn’t it possible that the embryo may develop in my uterus, but may not develop in the incubator ? Can I afford to take this risk ? This is true, which is why many IVF labs will transfer embryos on Day 2 or 3 , and refuse to do a blastocyst transfer , if you grow few eggs. This is because the end point of an IVF cycle for the clinic is an embryo; and if they have made embryos for you, they are satisfied, because they have successfully accomplished their task. Patients are happy with IVF clinics when they can make good embryos for them !

However , for the patient , the end point is not an embryo, but a baby ! A good clinic and a smart patient will have the courage to grow the embryos to blastocyst in the incubator, even if you grow few eggs . This is because if you do transfer your embryos into your uterus on Day 2, and you do not get pregnant, you will never know if the reason for the failed implantation was because your embryos were not capable of growing and developing further; or if because your endometrium was not receptive . If you had tried to grow them to blastocyst in the incubator, and they had arrested in vitro, this means they would have arrested in your uterus as well, and would never have implanted in any case ! By not allowing them to grow to the blastocyst stage, you have just subjected yourself needlessly to the dreaded 2ww of anticipation and fear . Even worse, you are no wiser for your next cycle, because you still do not know if your embryos are capable of forming blastocysts or not !

For patients with recurrent implantation failure , growing embryos up to the blastocyst stage provides a lot of useful information . If your embryos do develop to blastocysts in the lab , you know that your embryo quality is reasonably okay . However , if all your embryos arrest on Day 4 and none of them form blastocysts , this means the problem is with your embryos and not with your uterus ; and that you would be far better off using donor eggs to get better quality embryos, rather than considering surrogacy ! On the other hand , if you transfer them all on Day 2 or Day 3, you may have the satisfaction that you reached the stage of embryo transfer, but this is likely to be a very short-lived satisfaction ! The downside is that if your cycle fails, you will still never be sure what to do for the next cycle , because you're not sure whether the reason for the failed implantation was a problem with the uterus , or a problem with your embryos.

1 comment:

Thank You very much for this post! I have a question-if laboratory culture conditions are not good then a cleavage stage embryo can get arrested without further development-right? So isn't it better to transfer the embryo on day 2 or day 3 inside their natural incubator? Especially, if there is no difference in the implantation rates of a blastocyst or a cleavage stage embryo!